TMEM179B

Chr 11

transmembrane protein 179B

NCBI Gene: 374395 ENSG00000185475 UniProt: Q7Z7N9

The TMEM179B protein is a transmembrane protein of unknown function. Biallelic mutations cause autosomal recessive intellectual disability with seizures and dysmorphic features. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance.

Research

Located in nuclear speck. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.18LOEUF

pLI 0.001

Z-score 1.17

OE 0.60 (0.33–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.84Z-score

OE missense 1.22 (1.06–1.40)

145 obs / 119.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.60 (0.33–1.18)

0≤0.351.4

Missense OE?1.22 (1.06–1.40)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 6 / 10.0Missense obs/exp: 145 / 119.1Syn Z: -0.62

Background carrier burden — how many people carry a rare variant somewhere in TMEM179B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

359 rare PASS variants

Rare truncating (LoF)

1 in 1,300

65 rare PASS variants

Rare synonymous (reference)

1 in 820

168 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM179B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 1,800
South Asian	~43k	1 in 100	1 in 1,000
Remaining (unassigned)	~30k	1 in 160	1 in 1,200
European (Finnish)	~27k	1 in 620	1 in 1,900
Admixed American	~22k	1 in 210	1 in 4,200
African / African American	~21k	1 in 180	1 in 1,800
East Asian	~20k	1 in 250	1 in 3,200
Ashkenazi Jewish	~13k	1 in 1,400	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 250	1 in 450

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓